Definition of L-phenylalanine biosynthesis
As rules and steps, or see full text
Rules
Overview: Phenylalanine biosynthesis in GapMind is based on MetaCyc pathways L-phenylalanine biosynthesis I (link), II (link), and III (link). Pathways I and III proceed via 3-phenyl-2-oxopropanoate, but with different amino acids providing the amino group for the conversion to phenylalanine. In pathway II, L-arogenate is the intermediate (the aminotransferase reaction occurs before the dehydratase reaction).
Steps
PPYAT: tyrosine:phenylpyruvate aminotransferase
cmutase: chorismate mutase
- Curated proteins or TIGRFams with EC 5.4.99.5
- HMM PF01817
- Comment: Chorismate mutase is usually fused to prephenate dehydratase, which makes it difficult to find this activity when it is fused to something else. As of March 2019, the PFam does not have any characterized members with other functions
- Total: 12 HMMs and 26 characterized proteins
preph-dehydratase: prephenate dehydratase
- Curated proteins or TIGRFams with EC 4.2.1.51
- UniProt sequence Q8A0T5_BACTN: RecName: Full=Prephenate dehydratase {ECO:0000256|ARBA:ARBA00021872}; EC=4.2.1.51 {ECO:0000256|ARBA:ARBA00013147};
- Ignore hits to items matching EC 4.2.1.91 when looking for 'other' hits
- UniProt sequence D4GRZ0: SubName: Full=Prephenate dehydratase {ECO:0000313|EMBL:ADE02290.1}; EC=4.2.1.51 {ECO:0000313|EMBL:ADE02290.1};
- Comment: prephenate dehydratase and arogenate dehydratase can be difficult to distinguish. BT3936 (Q8A0T5_BACTN) is diverged but has auxotrophic phenotypes (as do homologs Echvi_0123, CA265_RS11630). HVO_0449 (D4GRZ0) is a phenylalanine auxotroph and is probably prephenate dehydratase (PMC4300041).
- Total: 21 characterized proteins
ilvE: phenylalanine transaminase
ptransferase: prephenate aminotransferase
- Curated proteins or TIGRFams with EC 2.6.1.79
- Curated proteins or TIGRFams with EC 2.6.1.78
- Ignore hits to items matching EC 2.6.1.5 when looking for 'other' hits
- Ignore hits to items matching EC 2.6.1.27 when looking for 'other' hits
- Ignore hits to items matching EC 2.6.1.57 when looking for 'other' hits
- Ignore hits to items matching EC 2.6.1.1 when looking for 'other' hits
- Comment: This enzyme forms arogenate, also known as pretyrosine.
- Total: 5 characterized proteins
aro-dehydratase: arogenate dehydratase
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About GapMind
Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using
ublast (a fast alternative to protein BLAST)
against a database of manually-curated proteins (most of which are experimentally characterized) or by using
HMMer with enzyme models (usually from
TIGRFam). Ublast hits may be split across two different proteins.
A candidate for a step is "high confidence" if either:
- ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
- HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.
where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").
Otherwise, a candidate is "medium confidence" if either:
- ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
- ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
- HMMer finds a hit (regardless of coverage or other bits).
Other blast hits with at least 50% coverage are "low confidence."
Steps with no high- or medium-confidence candidates may be considered "gaps."
For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways.
For diverse bacteria and archaea that can utilize a carbon source, there is a complete
high-confidence catabolic pathway (including a transporter) just 38% of the time, and
there is a complete medium-confidence pathway 63% of the time.
Gaps may be due to:
- our ignorance of proteins' functions,
- omissions in the gene models,
- frame-shift errors in the genome sequence, or
- the organism lacks the pathway.
GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).
For more information, see the paper from 2019 on GapMind for amino acid biosynthesis, the paper from 2022 on GapMind for carbon sources, or view the source code, or see changes to Amino acid biosynthesis since the publication.
If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know
by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory